Classic psychedelics linked to lasting increases in openness and drops in neuroticism

A recent systematic review published in the Journal of Psychopharmacology suggests that using classic psychedelics is linked to lasting changes in personality traits, particularly an increase in openness and a decrease in neuroticism. The comprehensive analysis of nearly 50 recent studies provides evidence that substances like psilocybin, LSD, and ayahuasca might shape human character in enduring ways.

Psychologists often understand human personality through the Five-Factor Model. This framework organizes personality into five broad categories. These are openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism.

Openness reflects curiosity, imagination, and a willingness to embrace new ideas. Conscientiousness involves self-discipline, organization, and goal-oriented behavior. Extraversion captures a person’s sociability, assertiveness, and energy levels.

Agreeableness describes a tendency toward empathy, cooperation, and concern for others. Neuroticism refers to how people handle negative emotions, with higher levels indicating a vulnerability to anxiety, mood swings, or depression.

While personality tends to be stable over a person’s lifetime, evidence indicates that life experiences and biology can shift these enduring traits. Biology and environmental influences interact to constantly adjust how personality traits are expressed. In recent years, scientists have focused on how classic psychedelics might influence these psychological categories.

Classic psychedelics include substances like psilocybin, LSD, mescaline, and ayahuasca. These drugs primarily interact with serotonin receptors in the brain, which help regulate mood, cognition, and perception. A previous review from 2018 examined early evidence of personality shifts linked to these substances.

Since then, the field of psychedelic science has grown substantially. The authors of the current paper aimed to update that older literature review. Rafael Guimarães dos Santos, a professor in the department of neuroscience and behavior at the University of São Paulo’s Ribeirão Preto Medical School in Brazil, helped lead the new analysis.

“The impact of classic psychedelics (5-HT2A receptor agonists, LSD, DMT, psilocybin) on personality traits has been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are linked to agonism at cortical serotonergic 5-HT2A receptors,” said dos Santos, who is also a member of the Phantastica Lab.

Agonism refers to a chemical binding to a receptor and activating it. In this case, the drugs activate specific serotonin receptors located in the outer layers of the brain. “For example, some studies have found increases in openness and decreases in neuroticism,” dos Santos added. “However, research results are contradictory.”

To resolve these contradictions, the researchers wanted to capture the recent surge in data. They were especially interested in studies looking at naturalistic drug use and microdosing. Naturalistic use refers to people taking psychedelics in real-world settings rather than in a laboratory. Microdosing involves taking very small, sub-hallucinogenic amounts of a drug on a regular schedule.

The scientists searched four major academic databases for articles published between January 2016 and early 2025. They screened over 6,000 scientific summaries to find research specifically looking at classic psychedelics and personality assessments. This process yielded 48 relevant studies.

The final collection included 14 experimental trials and 34 observational studies. Experimental trials take place in controlled laboratory or clinical settings, often using placebo comparisons to test specific drug doses. Observational studies track people who are already using these substances on their own.

Across the 48 papers, sample sizes varied widely. Some clinical trials featured fewer than 20 participants, while a few online surveys gathered data from thousands of recreational users. Most of the included studies relied on questionnaires based on the Five-Factor Model to measure personality traits, though some used alternative psychological frameworks.

When synthesizing the data, the researchers found a few consistent patterns. People who use psychedelics long-term share similar personality profiles, and the substances themselves appear to promote these shifts.

“The most consistent findings were, indeed, increases in Openness and reductions in Neuroticism, especially with psilocybin and ayahuasca,” dos Santos told PsyPost. “Changes in other traits, such as Extraversion, Agreeableness, and Conscientiousness, were more variable. However, controlled studies are few, and limited by number of doses and difficult to compare to real-world scenarios of use.”

Observational data indicates that experienced users tend to score unusually high in openness and low in neuroticism. In some populations, such as groups that use ayahuasca in traditional religious ceremonies, individuals also exhibit higher levels of agreeableness and self-transcendence. Self-transcendence is a psychological concept related to feeling connected to the wider universe, spiritual acceptance, and a sense of unity with nature.

A person’s baseline personality tends to predict how they will react to a psychedelic drug. Participants with naturally high openness scores are more likely to have positive, deeply meaningful experiences during a psychedelic trip. Individuals with high levels of neuroticism or impulsivity are more prone to challenging, anxious, or frightening psychological reactions. This finding highlights how a person’s starting mindset can shape their response to powerful psychoactive compounds.

The review provides evidence that taking psychedelics under controlled conditions can cause lasting personality changes. In clinical trials involving psilocybin, which is the active compound in “magic mushrooms,” participants consistently showed reductions in neuroticism and increases in openness. These psychological shifts often remained stable for months after the drug was administered. In some clinical studies, patients treated with psilocybin also showed modest increases in extraversion.

Similar long-term effects were noted in controlled trials testing LSD. Healthy volunteers and patients who received LSD in experimental settings showed sustained drops in neuroticism. Following the LSD sessions, these individuals also displayed increased extraversion and conscientiousness when evaluated up to a year later.

The findings regarding ayahuasca were a bit more mixed in the experimental settings. While observational studies heavily linked ayahuasca use to higher openness and lower neuroticism, controlled clinical trials did not always replicate these exact results. One controlled trial found increased openness after ayahuasca administration, but other trials found no significant changes in personality traits. The scientists suggest that variations in the chemical makeup of different ayahuasca brews might contribute to these inconsistent results.

The review also looked at the practice of microdosing psychedelics, which was predominantly studied through observational surveys. The authors found that people who routinely microdose report modest reductions in neuroticism and higher levels of absorption. Absorption is a trait that describes how easily a person becomes fully engaged in sensory or imaginative experiences. Changes in other traits like extraversion or conscientiousness were less consistent across the microdosing literature.

While the collected data points toward psychedelics shaping personality, the authors note a few potential misinterpretations and limitations. Because a large portion of the review relies on observational studies, scientists cannot definitively prove cause and effect in those specific cases.

“Data is difficult to interpret, because there are several study designs, and maybe some people already have different personality traits at baseline that could already be related to hallucinogen use,” dos Santos said. “(For example, people with baseline high traits of openness to experience or neuroticism could be more inclined to take psychedelics.)”

Observational surveys often rely on self-reported data, which can be influenced by personal biases and expectations. If a person expects a drug to make them more empathetic or open-minded, they might rate themselves higher on those traits after taking it. Experimental trials offer more rigorous evidence to counteract this issue. However, laboratory trials often feature small sample sizes and highly selected participant pools, making it difficult to generalize the findings to the broader public.

Future research would benefit from combining controlled experimental procedures with long-term naturalistic tracking. The authors suggest using longer follow-up periods to see if personality shifts truly endure over many years. They also recommend utilizing more diverse personality questionnaires to capture individual differences that the standard models might miss.

Expanding these research methods will help scientists better understand exactly how psychedelics alter human character, which can provide a more accurate guide for clinical applications. To build on this systematic review, the research team is actively expanding their focus. “We are now exploring these variables in clinical populations, since most studies are in healthy volunteers,” dos Santos said.

The study, “Classic psychedelics and personality: An updated systematic review,” was authored by Anna Beatriz Vicentini, Caio César de Paula, José Augusto Silva Reis, José Carlos Bouso, Jaime E. C. Hallak, and Rafael G. dos Santos.